The purpose of this project is to define the humoral and cellular immune responses that relate to immunopathology, protective immunity and immunodiagnosis of patients with filariasis. Though qualitative differences do exist in the IgE antibody responses of patients with different clinical manifestations of filariasis, more impressive are the quantitative differences in IgE responses. Recent attention, therefore, has turned to regulatory mechanisms of IgE antibody production. Blood mononuclear cells from helminth infected patients spontaneously produce abundant IgE in vitro in contrast to those from normals or atopic individuals. Work is now aimed at defining T-cell regulatory factors that can affect IgE synthesis. IgG antibodies that block immediate hypersensitivity responses to parasite antigen have been described, and their pathogenetic significance is under study. The possibility that they are restricted to a single IgG subclass has led to detailed analysis of the IgG antibody response. Filariasis patients have a significantly greater proportion of their total and parasite antigen specific IgG as IgG4 (with less IgG1) than normals. Furthermore, the greatest percent of IgG4 specific antibodies were found in microfilaremic and T.E. patients. The significance of these unusual findings is under study. Use of qualitative techniques such as immunoblotting and immunoprecipitation has allowed visualization of antigens and allergens recognized by individual patients with filarial and other helminth infections. Attempts to define parasite specific antigens and to develop monoclonal antibodies to them for use in immunodiagnosis (ID) are in progress. Additional ID studies to detect circulatory antigens in parasitized individuals have resulted thus far in assays that can detect antigen in situations where antibody concentrations are relatively low; current efforts are directed toward modifying these techniques to detect antigens obscured because they are bound tightly in immune complexes.